I, Rodent

by Maud NewtonJanuary 5, 2016

by Maud Newton

Last year started with fluey nightmares about mice. I dreamed of mice used in research to benefit humans: “frantic” mice, for studying anxiety; “Methuselah” mice, known for longevity; and mice with human liver cells and brain cells and tumor cells. I also dreamed of mice that, as far as I know, exist only in my mind — mice with human lungs, brains, or hearts growing out of their bodies to replace our worn-out organs.

If you’ve been on the internet for a while, you’ve probably seen that photo of a lab mouse with a human ear jutting out of its back. Controversy about genetic engineering raged after it first made the rounds in the late nineties, but researchers were quick to note that the mouse was a naturally occurring immunocompromised mouse, a “nude mouse”, and not genetically modified. (It did have cow cartilage implanted beneath the skin in the shape of an ear, though.)

Nude mice, and others like them, were used in research until scientists engineered more severely immunocompromised mice, some of which are “knockout mice” whose manufacturers inactivate selective genes based on the type of research they’re intending to do.

I was eleven and visiting a friend who was about fourteen when some of her even-older friends showed up. “If you were an animal,” one of the boys told her, “you’d be a lynx.” He was handsome, with an easy, generous smile, and he continued around around the circle. This friend was a zebra, that friend was a grizzly, the next was a fox.

Eventually he reached me, took in my pale skin, my freckled face, my enormous brown glasses. “You’d be a mouse,” he said. I wanted to turn over the coffee table and throw a lamp against the wall, quash his judgment with ten seconds of fury. Instead I smiled regretfully and nodded. I wasn’t up to a scene and objecting politely would only confirm his opinion of me.

Growing up, I was often compared to mice, usually because I was quiet, but also because I was small. I heard it to mean that I didn’t register, that I was doomed to insignificance and anonymity.

Before I started having the nightmares, I’d been reading about mice used in human research for years. Generally, I exposed myself to stories about them in the way many of us do: Transfixed but cringing, curious about the science, flummoxed by the advent of such potentially dystopian experiments, hopeful for people who might be helped by the research, sad for the mice themselves. After reading, I quickly clicked away to something less fraught.

Last December brought a wave of reports about mice infused with human brain cells. They were vastly smarter than their mouse-brained counterparts, said the researchers. Nevertheless, the researchers contended, the brains of the engineered mice were still fundamentally mouse brains, not human brains, because the parts devoted to thinking consisted entirely of mouse cells.

Though I didn’t enjoy being compared to them, I always liked mice. When I was eight or nine, my mom gave me two, one black and one white. Despite the assurances of the pet store clerk, they were not both boys. Soon I had ten mice, in different colors. I separated them, males in one wire-covered aquarium and females in the other. The males chased each other around the cage and bit each other’s genitals. This was normal, my mom assured me.

A favorite friend visited from California. We took all the mice out to play and they got loose in the room. Every last one went into hiding. I worried they’d be eaten by our cats or that they’d live in the walls and procreate endlessly. I lay awake and imagined them cowering and shitting behind bookcases. Their interchangeability troubled me; I’d given them names but sometimes got them confused. If only a few came back, would I know for sure which ones they were? I left food out and somehow within six days I’d recaptured them all.

A week or two later, reckless with triumph, I took all the mice out again. Again, they got away. This time, after I gathered them up, my mom took them to the pet store and left them. She suggested this solution, and I quickly agreed, or maybe it was the other way around. In bed at night I tried not to imagine them, their bodies trembling, hearts racing with terror, as they ran from someone’s pet snake.

According to New Scientist, the researchers put human brain cells into mice by injecting ”immature glial cells” from human fetuses into baby mice, where they ”developed into astrocytes, a star-shaped type of glial cell,” and became invasive.

“Within a year, the mouse glial cells had been completely usurped.… The 300,000 human cells each mouse received multiplied until they numbered 12 million, displacing the native cells. ‘We could see the human cells taking over the whole space,’ [said the lead researcher]. ‘It seemed like the mouse counterparts were fleeing to the margins.’”

Astrocytes, the story notes, “are vital for conscious thought.”

A year after my friend’s friend said I was a mouse, my parents had divorced and my mom had remarried. Somehow we had a new white mouse, only one this time. My stepsister’s cousin, who was about six years old, put the mouse in her shoe and then put the shoe on.

“Take it off! Take it off!” my stepsister and I screamed.

After a couple minutes, the cousin’s mother intervened. The shoe came off and the mouse came out. It lay limp in the cousin’s hand.

Last year, the researchers who made mouse brains part-human were eager to try the same experiments in rats, which are considered naturally more intelligent than mice.

The team chose not to try the experiments on monkeys, however. ”’We briefly considered it but decided not to because of all the potential ethical issues,’” the lead researcher said.

Some months after the mouse suffocated in the shoe, we — my mom, stepfather, sister, stepsister, and I — moved to a house behind a shopping center with restaurant dumpsters that attracted vermin. My sister and I refer to this place as “the first rat house.”

The rats already had a stronghold when we moved in, and their fortifications grew with time. They only came out at night, and only in the kitchen, probably because it was out of reach of our dogs, who patrolled the place during the day but were sequestered with my mom and stepfather when it got late.

On the kitchen counters, in the sink, across the floor, the rats teemed and scrabbled. The room was papered in demonic red-and-white toile, its garish red cabinets and scuffed scarlet linoleum accentuating the surrealist horror movie vibe.

During the year we lived in the first rat house, my mom got two cockatiels. Within weeks she had twenty. Soon she branched out into parrots, parakeets, and finches. Eventually I realized that the rats flourished during our time in the first rat house because of the birds’ droppings and the husks of their feed.

On a webpage titled, “Why mouse genetics?” the company explains, “humans and mice are surprisingly similar. We share more than 95 percent of our genomes and get most of the same diseases…. A mouse with a specific disease or condition can serve as a model or stand-in for a human patient with that same disease or condition. This allows scientists to conduct experiments that would be ethically impossible in people.”

When we moved into the second rat house, it wasn’t a rat house yet. It had a pool and jacuzzi and, in several rooms, mirrored velvet seventies wallpaper. By that time my mom had accumulated more than a hundred birds. A few lived in our house; more lived in the yard; most lived on the back screened-in porch.

It must have been impossible for any self-respecting rodent to resist the bounty of spent kernels, plucked corncobs, and continually-flowing birdshit our house had to offer. By then we also had about ten dogs and after our boxer and Westie swallowed a few of the more intrepid rats whole, the rats of the second rat house, like those of the first, only came out at night and only in the kitchen.

If I needed something to eat after midnight, I liked to give them plenty of time to hide. I’d stomp to the threshold, reach quickly around the corner to turn on the light, and bang away for a bit. Then I’d return with even more noise, hoping they’d all have dispersed. Sometimes I saw them lumbering down from the sink, rushing to their mysterious tunnel under the cabinets.

In one of my favorite short stories, E.B. White’s “The Door,” a man ponders rats that a professor has “driven crazy by forcing them to deal with problems which were beyond the scope of rats, the insoluble problems” stemming from seemingly simple questions such as, which door leads to food and which leads to a shock.

Then the man catches “a glimpse of his eyes staring into his eyes, and in them was the expression he had seen in the picture of the rats — weary after convulsions and the frantic racing around, when they were willing and did not mind having anything done to them.”

I have no idea how many rats there were in the second rat house. Let’s just say, very very many. While I was away at college, my stepfather discovered that they’d eaten through concrete and established an enormous nest beneath the garbage disposal. He cemented the area back up, but even this didn’t eliminate them.

By the end of my family’s time in the house, I was in my mid-twenties and living elsewhere. Some of the rats had grown to the size of housecats. When I visited and deployed the lights-and-clattering gambit, they just leered at me from the counter.

So far, whatever discussion exists in the scientific community about how humanized mice themselves might be affected by, for example, having human brain cells, seems to focus on the ways we’ve succeeded in making the mice more like us.

Late last year, I read George Church’s Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves. As I wrote a few months afterward, the book is fascinating and repellent, brilliant and facile. It inspired my research into lab mice and my nightmares about them.

After I tweeted about humanized mice and linked to a site that sells knockout rodents, ads for genetically modified mice started following me around the internet.

I only encountered rodents in the wild — by which I mean, outside a pet store or my own home — with any regularity when I moved to Brooklyn at age twenty-eight. At night in the subways, the rats ran along the tracks, eating fallen Cheetos, licking soda straws, playing and fighting with each other.

Most things about the city are disharmonious with the timid animal part of myself I tend to disavow. There’s far too little nature and far too much noise, and it’s dirty and crowded and brash. But it’s taught me things.

I was too nice when I moved here, in a compulsive way. If someone seemed to take a dislike to me, I couldn’t stand it. Unless they were nasty enough to make my aggressive side kick in, I would keep trying to charm them, to show how genuine I was, how helpful I was, how well-intentioned. I met a woman who would later become one of my best friends, but who took a dislike to me because I wouldn’t stop doing this kind of scrambling. The harder I tried, the more chilly her responses. Much later, after we’d become close, we talked about the night we first met.

“You were like a hamster in a wheel,” she said, putting her hands up and paddling to signify running. “Squeak squeak, squeak squeak.” Nowadays she hates that she said this, but it was one of the most helpful things anyone has ever told me. After that, whenever I found myself hamster-wheeling, I knew I needed to stop. I tried to focus on my Cheetos, lick my straw.

Humanized mice give us hope of freedom from illness, from fear, from the inevitability of death. These are all things I was taught as a child that believing in Jesus could do. In the Bible story, though, the son of God chooses to become human.

Several years ago, my father-in-law died of multiple myeloma. In August, one of my best friends died of diffuse B Cell lymphoma. Both of them lived longer than they otherwise might have because of experimental chemo that was likely honed through research on knockout mice.

Former president Jimmy Carter announced last month that he’s free of tumors that were in his brain and liver earlier this year. He was given the experimental drug Keytruda, which was tested on syngeneic mouse models.

We’ve engineered rodents to take on diseases for us, to suffer so that we might be healthier and happier and live longer. Because of this, some of us have extra time on the planet. And also, because of this, lab mice exist in myriad permutations, many of them miserable.

We have brought these creatures into being. What are our responsibilities to them?

For a couple years I’ve been studying the Alexander Technique. I started because I had bad posture and a racing overanxious brain and nothing else I’d tried until then (apart from psychotherapy) had helped much with either.

The Alexander Technique is difficult to describe, but it can teach you to reduce unnecessary tension by becoming aware of your habits, of things that have come to seem inherent to an activity but aren’t really. For example, thinking doesn’t actually entail clenching your jaw or wrinkling your forehead, even if you always do those things when you’re concentrating. Sitting doesn’t need to involve swinging your arms. Texting doesn’t have to induce hunching.

Something you can do to try to train yourself out of habits like these is to tell yourself things like, “I am not sitting down,” even as you sit down, and see what happens. Or tell yourself, “thinking is not a jaw activity,” or even, “I don’t have a jaw.”

I’m describing it poorly, but the Alexander Technique has acquainted me with so many knotty places in myself that I can work with more easily now. One that remains mysterious is just below my chest, between my heart and my gut. It’s a spot that always feels kinked.

“Sometimes it helps to imagine what it feels like to be inside there,” my teacher said recently.

I’ve learned to take these suggestions seriously and when I got home later I tried feeling my way into the spot. It was hard like a walnut on the outside. The thunder of my heartbeat reverberated all around. Prying open the nut, I found a small brown mouse, trembling and uncertain, its whiskers twitching. It was braced to hamster-wheel. It expected to be disavowed. It’s okay, little mouse, I thought, and the kink loosened slightly.

This essay has been edited to reflect the distinction between humanized mice and knockout mice used in human research.